Study on stigmasterol, an active component of lily extract, inhibits reflux esophagitis by targeting TBXAS1
Keywords:
Network pharmacology, stigmasterol, TBXAS1, molecular dynamics simulation, gastroesophageal reflux disease, GERDAbstract
Gastroesophageal reflux disease (GERD) is a prevalent digestive disorder characterized by esophageal mucosal inflammation, with a potential risk of progressing to esophageal adenocarcinoma. Lilium brownii, a traditional medicinal herb, exhibits significant anti-inflammatory properties; however, the molecular mechanism of its active components in treating GERD remains largely elusive.
Methods. In this study, we employed an integrated strategy combining network pharmacology, molecular docking, and molecular dynamics (MD) simulations to investigate the therapeutic potential of stigmasterol, a major phytosterol in lilium brownii. The core targets were identified via TCMSP, Genecards, and Disgenet databases. The binding affinity and structural stability of the stigmasterol-TBXAS1 complex were evaluated using Autodock vina and Gromacs (100 ns). Furthermore, the pharmacological effects were validated in vitro through western blot and cellular apoptosis assays.
Results. Network analysis revealed that TBXAS1 (thromboxane A synthase 1) is a critical hub protein involved in GERD-related inflammatory cascades. Molecular docking demonstrated a high binding affinity of −8.7 kcal/mol, characterized by stable hydrophobic interactions and hydrogen bonding within the catalytic pocket. Md simulations confirmed the stability of the complex, with a root mean square deviation (RMSD) consistently below 2.0 å. In vitro experiments evidenced that stigmasterol significantly down-regulated TBXAS1 expression and inhibited cell proliferation in a dose-dependent manner. ADMET profiling via SwissADME (boiled‑egg model) indicated superior gastrointestinal absorption and a favorable safety profile compared to omeprazole.
Conclusion. Our findings elucidate that stigmasterol exerts its protective effects against GERD by targeting the TBXAS1-mediated pathway. This study provides a novel theoretical framework for developing lilium-derived bioactive compounds as targeted therapeutic agents for esophageal inflammatory diseases.
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